The Role of the Integrin-linked Kinase (ILK) in Mammary Gland Tumorigenesis and Metastasis

Abstract

The research objective outlined in the original proposal was to determine the role of the integrin-linked kinase (ILK) in the induction and progression of metastatic mammary tumors. This work was initially based on the observation that overexpression of ILK in cultured epithelial cells results in changes characteristic of oncogenic transformation (Hannigan et al, 1996; Novak et al., 1998; Radeva et al., 1997; Wu et al., 1998). In order to evaluate the oncogenic potential of ILK in the mammary gland, we derived transgenic mice that express ILK under the transcriptional control of the MMTV promoter. The appearance of focal mammary tumors in these MMTV/ILK mice confirms that mammary-specific expression of ILK can facilitate malignant transformation in vivo. A second major objective was to determine the role of ILK in tumor progression by ablating its function. For this purpose, we established transgenic mice expressing a kinase-dead allele of ILK in the mammary epithelium. We are currently breeding these mice with our MMTV/erbB-2 strains to assess the importance of ILK in erbB-2-mediated mammary tumorigenesis and metastasis. This last experiment is particularly relevant to the understanding and treatment of human breast cancer, given the known importance of erbB-2 in the progression of this disease.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2000
Accession Number
ADA384019

Entities

People

  • Donald E. White
  • William A Muller

Organizations

  • McMaster University

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Cytoskeleton
  • Diseases And Disorders
  • Epithelial Cells
  • Epithelium
  • Glands
  • Integrins
  • Mammary Glands
  • Medical Personnel
  • Metastasis
  • Neoplasms
  • Tissues

Readers

  • Molecular Biology and Genetics